TL;DR
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Research on cancer risk in people with sickle cell disease (SCD) has produced mixed results. A recent review found an overall signal of increased malignancy, particularly blood cancers, but experts say the size and cause of any added risk remain unsettled; new laboratory findings on clonal blood-cell growth may offer clues.
A MedPage Today report published October 15, 2026, says evidence linking sickle cell disease (SCD) to cancer remains mixed, even as newer laboratory studies point to a possible difference in clonal blood-cell growth. Some studies have found higher rates of blood cancers among people with SCD, but researchers say the overall size and cause of any added risk are not established.
Population studies have reached different conclusions. A British study of more than 7,500 people with SCD reported about twice the risk of any malignancy compared with its reference population, including several blood cancers and solid cancers. A California study of 6,400 people found a lower overall cancer risk, alongside a 72% higher leukemia risk and a 38% lower risk of solid cancers. A case-control study of about 1,300 people found no overall increase or increase in solid tumors, but reported a marginal rise in blood cancers.
A systematic review covering approximately 24,000 patients worldwide found highly variable risk estimates. Its pooled findings pointed to increased malignancy in SCD and thalassemia, particularly hematologic cancers and, in SCD, myeloid leukemia. Those findings do not resolve the disagreement among individual studies, and the report says the absolute risk of malignancy remains low.
Fresh interest in the question followed two cancers reported during trials of the SCD gene therapy lovotibeglogene autotemcel (lovo-cel): leukemia in one patient and myelodysplastic syndrome in another. The trials were paused. The manufacturer, Bluebird Bio, said an investigation found the treatment was “very unlikely” to have caused the cases; the FDA later lifted the hold and approved lovo-cel. Its prescribing information carries a boxed warning about potential malignancy risk. The report notes that high-dose chemotherapy used with gene therapy and stem-cell transplantation is another concern raised by a treating physician, but that is distinct from evidence that SCD itself causes cancer.
Cancer Risk Shapes SCD Care
The uncertainty matters to people with SCD weighing treatment options and to clinicians discussing risks over a lifetime. Gene therapy labeling includes a malignancy warning, while the earlier trial pause brought public attention to cancers occurring during treatment. At the same time, the evidence does not establish that SCD itself makes cancer likely, or that a particular treatment caused the reported cases.
Clearer estimates could help inform risk discussions and long-term monitoring. For now, the source report presents a cautious picture: possible excess risk, with the strongest recurring signal in blood cancers, but no settled estimate of how large that risk is or which factors account for it.
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Studies Point in Different Directions
Early reports, including case reports and survey-based studies, generally suggested higher cancer rates in SCD. Later population studies produced more varied results, partly reflecting differences in populations, study design and cancer categories. A separate study of sickle cell trait (SCT) found no significant overall association with cancer, though researchers reported a lower leukemia risk than in SCD and a trend toward higher kidney-cancer risk. Trait and disease are not interchangeable conditions.
Researchers have also examined whether SCD should be viewed as a cancer-predisposition syndrome. A review discussed in the report concluded that the relative risk appears much lower than in established cancer-predisposition syndromes and closer to risks associated with common genetic variations. Another concern—whether hydroxyurea raises cancer risk—was described by a physician as having been refuted. These distinctions matter because an association in some datasets does not identify a cause.
““There appears to be an increased malignancy risk in sickle cell disease” but “the extent to which there is an increased malignancy risk remains not so well established.””
— Vijay Sankaran, MD, PhD, Harvard Medical School and Boston Children’s Hospital
How Large Is Any Added Risk?
Researchers have not established whether SCD independently raises overall cancer risk, how large any increase might be, or why results differ across studies. The evidence points more consistently toward blood cancers than solid tumors, but estimates vary. The report also does not provide enough detail to determine how much differences in age, treatment exposure, follow-up or study methods explain that variation.
The newer clonal-hematopoiesis findings are a possible clue, not proof of a pathway from SCD to cancer. One sensitive-assay study found four times higher odds of clonal hematopoiesis in two cohorts of children with SCD than in matched controls. The report excerpt does not provide the results of the other study it mentions, so its findings cannot be summarized here. It is also unclear how the laboratory finding relates to cancer outcomes in patients.
For gene therapy, the report says investigators concluded the treatment was very unlikely to have caused the trial cancers, but it does not supply the full investigation or supporting data. A cancer occurring during treatment does not by itself establish that the treatment caused it. The relative contributions of SCD, treatment exposures and other factors remain unresolved.
Further Studies Must Clarify Risk
The next step is more research capable of comparing cancer outcomes across well-defined SCD populations and suitable control groups, while accounting for age and treatment exposures. More sensitive tests for clonal hematopoiesis may help researchers understand whether blood-cell clones are more common in SCD and whether they predict later malignancy. Those laboratory results will need to be connected to clinical outcomes before they can explain cancer risk.
People considering gene therapy or transplantation will also need continued study of long-term outcomes and clear discussion of the risks described in product information. The report does not identify a specific upcoming study result or regulatory decision. Until stronger evidence is available, clinicians and patients must weigh established treatment information alongside an uncertain baseline cancer-risk estimate.
Key Questions
Does sickle cell disease definitely increase cancer risk?
No definitive answer has been established. Some studies and a systematic review suggest increased malignancy, particularly blood cancers, while other population studies found no overall increase or lower overall rates.
Which cancers have been most associated with SCD?
The most consistent signal in the report concerns hematologic cancers, especially myeloid leukemia. Studies have differed on overall cancer risk and on solid tumors.
Did the SCD gene therapy cause the cancers reported in trials?
Bluebird Bio said its investigation found lovo-cel was “very unlikely” to be the cause. The FDA later lifted the trial hold. The report does not provide enough investigation detail to independently assess the conclusion.
What is clonal hematopoiesis, and why is it being studied?
It occurs when acquired mutations allow some blood stem cells to multiply faster than others, creating cell populations called clones. Sensitive testing has found higher odds of the condition in children with SCD in one study, but its connection to cancer outcomes is not established.
Does sickle cell trait carry the same reported cancer risk as SCD?
No. A study described in the report found no significant overall cancer association with sickle cell trait. Trait and sickle cell disease are different conditions, and the findings should not be treated as interchangeable.
Source: rss
